Resveratrol Does Not Influence Metabolic Risk Markers Related to Cardiovascular Health in Overweight and Slightly Obese Subjects: A Randomized, Placebo-Controlled Crossover Trial
March
Resveratrol Does Not Influence Metabolic Risk Markers Related to Cardiovascular Health in Overweight and Slightly Obese Subjects: A Randomized, Placebo-Controlled Crossover Trial
Sanne M. van der Made 0 1
Jogchum Plat 0 1
Ronald P. Mensink 0 1
0 1 Department of Human Biology, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Center , Maastricht , The Netherlands , 2 Top Institute of Food and Nutrition (TIFN) , Wageningen , The Netherlands
1 Academic Editor: Giuseppe Danilo Norata, University of Milan , ITALY
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Funding: The project is funded by TI Food and
Nutrition, a public-private partnership on
precompetitive research in food and nutrition. The
public partners are responsible for the study design,
data collection and analysis, decision to publish, and
preparation of the manuscript. Trans-resveratrol
In vitro and animal studies have shown positive effects of resveratrol on lipid and lipoprotein
metabolism, but human studies specifically designed to examine these effects are lacking.
The primary outcome parameter of this study in overweight and slightly obese subjects was
the effect of resveratrol on apoA-I concentrations. Secondary outcome parameters were
effects on other markers of lipid and lipoprotein metabolism, glucose metabolism, and
markers for inflammation and endothelial function.
This randomized, placebo-controlled crossover study was conducted in 45 overweight and
slightly obese men (n = 25) and women (n = 20) with a mean age of 61 7 years. Subjects
received in random order resveratrol (150 mg per day) or placebo capsules for 4 weeks,
separated by a 4-week wash-out period. Fasting blood samples were collected at baseline
and at the end of each intervention period.
Compliance was excellent as indicated by capsule count and changes in resveratrol and
dihydroresveratrol concentrations. No difference between resveratrol and placebo was
found in any of the fasting serum or plasma metabolic risk markers (mean SD for
differences between day 28 values of resveratrol vs. placebo: apoA-I; 0.00 0.12 g/L
(P = 0.791), apoB100; -0.01 0.11 g/L (P = 0.545), HDL cholesterol; 0.00 0.09 mmol/L
capsules were provided by DSM Nutritional Products
Ltd. (Kaiseraugst, Switzerland).
Competing Interests: The funding we received from
TI Food and Nutrition and the capsules that were
given by DSM Nutritional Products Ltd. does not alter
the authors adherence to PLOS ONE policies on
sharing data and materials.
(P = 0.721), LDL cholesterol -0.03 0.57 mmol/L (P = 0.718), triacylglycerol; 0.10 0.54
mmol/L (P = 0.687), glucose; -0.08 0.28 mmol/L (P = 0.064), insulin; -0.3 2.5 mU/L
(P = 0.516)). Also, no effects on plasma markers for inflammation and endothelial function
were observed. No adverse events related to resveratrol intake were observed.
150 mg of daily resveratrol intake for 4 weeks does not change metabolic risk markers
related to cardiovascular health in overweight and slightly obese men and women. Effects on
glucose metabolism warrant further study.
ClinicalTrials.gov NCT01364961
The many approaches that exist to lower cardiovascular risk are mainly aimed at lowering LDL
cholesterol concentrations. Based on epidemiological studies [14], increasing HDL cholesterol
concentrations may also reduce cardiovascular risk, but this concept has been challenged by
intervention studies [57]. However, a recent meta-analysis has suggested that increasing
apolipoprotein A-I (apoA-I) concentrations is a more important target to reduce the risk of major
cardiovascular events than increasing HDL cholesterol concentrations [8]. ApoA-I is the major
protein constituent of the HDL particle, which plays a crucial role in many of the favorable
effects attributed to HDL particles, includingnext to their fundamental role in reverse
cholesterol transportanti-inflammatory, anti-thrombotic and anti-oxidative effects [9,10].
Epidemiological studies have shown a positive association between higher polyphenol
intakes and reduced cardiovascular risk [11,12]. This association may be due to increased intakes
of trans-resveratrol (3,5,4-trihydroxystilbene), a polyphenol found in the skin of black grapes.
Resveratrol may influence numerous mechanisms, which act on the progression as well as on
the regression of atherosclerosis [13]. In fact, in vitro and animal studies have shown many
positive effects of resveratrol on genes and proteins involved in lipid and glucose metabolism,
including increases in the activities of peroxisome proliferator-activated receptor (PPAR)
and PPAR [14,15].
While the results from in vitro and animal studies are promising, and an HDL cholesterol
elevating effect of berries [16] and red wine [17], both of which contain resveratrol, has been
reported, human studies with the primary aim to examine the effects of resveratrol on lipid and
lipoprotein metabolism are scarce. Furthermore, human data onto the effect of resveratrol on
markers for metabolic risk is limited an (...truncated)